Department of Clinical Sciences Lund, Rheumatology, Lund University and Skåne University Hospital, Lund, Sweden.
Department of Autoimmunology & Biomarkers, Statens Serum Institute, Copenhagen S, Denmark.
Rheumatology (Oxford). 2021 Dec 24;61(1):309-318. doi: 10.1093/rheumatology/keab300.
SSc-associated pulmonary arterial hypertension (SSc-APAH) is a late but devastating complication of SSc. Early identification of SSc-APAH may improve survival. We examined the role of circulating miRNAs in SSc-APAH.
Using quantitative RT-PCR the abundance of mature miRNAs in plasma was determined in 85 female patients with ACA-positive lcSSc. Twenty-two of the patients had SSc-APAH. Sixty-three SSc controls without PAH were matched for disease duration. Forty-six selected miRNA plasma levels were correlated with clinical data. Longitudinal samples were analysed from 14 SSc-APAH and 27 SSc patients.
The disease duration was 12 years for the SSc-APAH patients and 12.7 years for the SSc controls. Plasma expression levels of 11 miRNAs were lower in patients with SSc-APAH. Four miRNAs displayed higher plasma levels in SSc-APAH patients compared with SSc controls. There was significant difference between groups for miR-20a-5p and miR-203a-3p when correcting for multiple comparisons (P = 0.002 for both). Receiver operating characteristics curve showed AUC = 0.69-0.83 for miR-21-5p and miR-20a-5p or their combination. miR-20a-5p and miR-203a-3p correlated inversely with NT-pro-Brain Natriuretic Protein levels (r = -0.42 and -0.47). Mixed effect model analysis could not identify any miRNAs as predictor of PAH development. However, miR-20a-5p plasma levels were lower in the longitudinal samples of SSc-APAH patients than in the SSc controls.
Our study links expression levels of the circulating plasma miRNAs, especially miR-20a-5p and miR-203a-3p, to the occurrence of SSc-APAH in female patients with ACA-positive lcSSc.
硬皮病相关性肺动脉高压（SSc-APAH）是硬皮病的一种晚期但具有破坏性的并发症。早期发现 SSc-APAH 可能会改善患者的生存率。我们研究了循环 miRNA 在 SSc-APAH 中的作用。
使用定量 RT-PCR 检测了 85 例 ACA 阳性局限型硬皮病女性患者血浆中成熟 miRNA 的丰度。其中 22 例患者患有 SSc-APAH，63 例 SSc 对照患者无肺动脉高压，两组患者的疾病持续时间相匹配。分析了 46 个选定的 miRNA 血浆水平与临床数据的相关性。对 14 例 SSc-APAH 患者和 27 例 SSc 患者进行了纵向样本分析。
SSc-APAH 患者的疾病持续时间为 12 年，SSc 对照组患者的疾病持续时间为 12.7 年。SSc-APAH 患者的血浆表达水平较低。与 SSc 对照组相比，SSc-APAH 患者有 4 种 miRNA 的血浆水平较高。校正多重比较后，miR-20a-5p 和 miR-203a-3p 两组间差异有统计学意义（P=0.002）。受试者工作特征曲线显示 miR-21-5p 和 miR-20a-5p 或两者联合的 AUC 值为 0.69-0.83。miR-20a-5p 和 miR-203a-3p 与 NT-pro-Brain Natriuretic Protein 水平呈负相关（r=-0.42 和-0.47）。混合效应模型分析未能确定任何 miRNA 作为肺动脉高压发展的预测因子。然而，在 SSc-APAH 患者的纵向样本中，miR-20a-5p 的血浆水平低于 SSc 对照组。
我们的研究将循环血浆 miRNA 的表达水平，特别是 miR-20a-5p 和 miR-203a-3p，与 ACA 阳性局限型硬皮病女性患者 SSc-APAH 的发生联系起来。
